Global cerebral ischemia, such as occurs during cardiopulmonary arrest or severe hypotension elicits a constellation of responses including increased systemic arterial pressure, bradycardia, shifts in regional blood flow, and apnea. These responses, collectively known as the cerebral ischemic response (CIR), appear to be integrated within the medulla. The present project will investigate in rabbits the central neuronal control of the CIR. Global cerebral ischemia will be elicited by briefly clamping both common carotid arteries after previously occluding the vertebral arteries. Extracellular single neuron recordings will be made before, during, and after the elicitation of diffuse cerebral ischemia in order to investigate the responses of: (a) intramedullary neurons along the pathways giving rise to the CIR; (b) cardio- and vaso-motor neurons in the medulla; and (c) descending supramedullary projections to the vaso0motor and cardio-motor neurons. The neuronal changes occurring during ischemia and during reperfusion will be correlated with changes in EEG, respiration rate and amplitude, core temperature, systemic arterial pressure, total peripheral resistance, heart rate, cardiac output and regional blood flow to the brain and other organs. Using 14C-iodoantiphyrine as the blood flow tracer, radioactivity will be measured from core samples of various organs and tissues (e.g., kidneys, heart, hind-limb muscle) including the bran; brain autoradiograms will also be prepared and subjected to microdensitometry for quantification of local cerebral blood flow. Neuronal and other physiological responses to global cerebral ishemia will be compared with responses to focal ischemia evoked by injection of 100 Mu plastic-coated carbonized microspheres into the internal carotid artery after prior occlsion of the vertebral arteries. The functional connections studied by extracellular single neuron recordings will also be correlated with morphologic data obtained using horseradish perioxidase reaction products and 14C-deoxyglucose as neuroanatomical tracers. Knowledge obtained about the central neuronal control of the circulation in response to cerebral ischemia and to reperfusion is likely to be helpful in the planning of circulatory management during and post ischemia.